Encouraging Clinical Responses in Early-Stage Breast Cancer with Immune-Modulating Radiation Therapy

Patients with early-stage ER+HER2− breast cancer showed improved clinical responses when durvalumab was added to neoadjuvant immune-modulating stereotactic body radiation therapy, according to a randomized phase 2 Neo-CheckRay trial published June 25, 2026, in Nature Medicine. These results included patients with PD-L1-negative tumors.

The Neo-CheckRay trial tested the efficacy of combining stereotactic body radiation therapy (SBRT) with immunotherapy agents in a specific subtype of breast cancer that is often less responsive to traditional checkpoint inhibitors. Researchers evaluated the impact of adding durvalumab, an anti-PD-L1 antibody, and oleclumab, an anti-CD73 antibody, to the radiation regimen.

How did the Neo-CheckRay trial function?

The study utilized a randomized phase 2 design to compare different treatment arms before the primary surgical intervention, a process known as neoadjuvant therapy. Patients with early-stage breast cancer that tested positive for estrogen receptors (ER+) and negative for human epidermal growth factor receptor 2 (HER2−) were enrolled.

According to the Nature Medicine report, patients received neoadjuvant immune-modulating SBRT. The trial randomized participants to receive this radiation therapy either alone, in combination with durvalumab, in combination with oleclumab, or with both immunotherapy agents.

The primary goal was to determine if these immune-modulating agents could enhance the clinical response of the radiation therapy in this specific cancer subtype.

What role did durvalumab and oleclumab play?

Durvalumab is designed to block the PD-L1 protein, which cancer cells use to hide from the immune system. By inhibiting this pathway, the drug allows T-cells to recognize and attack the tumor.

Oleclumab targets CD73, an enzyme that produces adenosine in the tumor microenvironment. According to the researchers, adenosine typically suppresses the immune response, and blocking CD73 with oleclumab aims to reverse this immunosuppression.

The trial found that the addition of durvalumab to the SBRT regimen led to encouraging clinical responses, according to the study findings published June 25, 2026.

Why is the response in PD-L1-negative tumors significant?

In many cancers, the presence of PD-L1 is used as a biomarker to predict whether a patient will respond to immunotherapy. Patients with PD-L1-negative tumors typically show lower response rates to drugs like durvalumab.

The Neo-CheckRay trial data indicated that durvalumab improved responses even in patients whose tumors were PD-L1-negative. This suggests that the immune-modulating effects of the SBRT may help sensitize the tumor to immunotherapy, regardless of the initial PD-L1 status.

How does this differ from standard ER+HER2− treatment?

ER+HER2− breast cancers are generally characterized as “cold” tumors, meaning they have low levels of immune cell infiltration. Because of this, they have historically responded poorly to single-agent checkpoint inhibitors compared to “hot” tumors, such as triple-negative breast cancer.

Standard treatment for this subtype typically focuses on endocrine therapy and chemotherapy. The Neo-CheckRay approach attempts to change the tumor microenvironment using SBRT to make the cancer more susceptible to the immune system.

By combining targeted radiation with antibodies like durvalumab and oleclumab, the researchers sought to convert these “cold” tumors into “hot” tumors that the immune system can actively fight.

What happens next for this research?

While the phase 2 results are described as encouraging, the researchers have not yet established these combinations as a standard of care. The trial provides a basis for further investigation into the optimal combination of radiation and immunotherapy for early-stage breast cancer.

Future studies will likely focus on the long-term outcomes of these patients and whether the neoadjuvant response translates to higher rates of complete pathological response or improved overall survival.